Mediator Systems of Lung Injury

  • P. E. Wright
  • G. R. Bernard
  • K. L. Brigham

Abstract

The lung responds to injury in a stereotypical fashion involving cellular and humoral mediators [7,18]. Regardless of the injurious agent, the same mediator systems can result in diffuse lung dysfunction or injury. Cellular mediators include polymorphonuclear leukocytes, lymphocytes, platelets and macrophages. Humoral mediator systems include the arachidonic acid cascade, histamine, kallikreins, coagulation cascade, interleukin-2 and complement. However, no one mediator system can explain all aspects of lung injury. Experimental evidence in animal models and human studies indicates that multiple mediators interact to result in diffuse lung injury regardless of the nature of the primary injury.

Keywords

Placebo Permeability Corticosteroid Superoxide Histamine 

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References

  1. 1.
    Bernard GR, Lucht W, Niedermeyer M, Snapper JR, Ogletree M, Brigham KL (1984) Effect of n- acetylcysteine on the pulmonary response to endotoxin in awake sheep and upon in vitro granulocyte function. J Clin Invest 73: 1772–1784PubMedCrossRefGoogle Scholar
  2. 2.
    Bernard GR, Luce JM, Sprung CL et al. (1987) High-dose corticosteroids in patients with ARDS. N Engl J Med 317: 1565–1570PubMedCrossRefGoogle Scholar
  3. 3.
    Bernard GR, Reines HD, Metz CA et al. (1988) Effects of a short course of ibuprofen in patients with severe sepsis. Am Rev Respir Dis 137: 138 (abstr)Google Scholar
  4. 4.
    Bihari D, Smithies M, Ginson A, Tinker J (1987) The effects of vasodilation with PGI2 (prostacyclin) on oxygen delivery and uptake in critically ill patients. N Engl J Med 317: 397–403PubMedCrossRefGoogle Scholar
  5. 5.
    Brigham KL, Meyrick BO (1984a) Reactions of granulocytes with the lungs. Circ Res 54: 623–625PubMedGoogle Scholar
  6. 6.
    Brigham KL, Meyrick BO (1984b) Granulocyte dependent injury of pulmonary endothelium: a case of miscommunication? Tissue Cell 16: 137–155PubMedCrossRefGoogle Scholar
  7. 7.
    Brigham KL, Meyrick BO (1986) Endotoxin and lung injury. Am Rev Respir Dis 133: 913–927PubMedGoogle Scholar
  8. 8.
    Brigham KL, Ogletree M (1981) Effects of prostaglandins and related compounds on lung vascular permeability. Bull Eur Physiopathol Respir 17: 703–722PubMedGoogle Scholar
  9. 9.
    Cochrane CC, Spragg RG, Rivak S, Cohen AB, McGuire WW (1983) The presence of neutrophil elastase and evidence of oxidant activity in the bronchoalveolar lavage fluid of patients with ARDS. Am Respir Dis 127(Suppl):25 - 27Google Scholar
  10. 10.
    Cook JA, Wise WC, Halushka P (1980) Elevated thromboxane levels in the rat during endotoxic shock: protective effects of imidazole, 13-azaprostanoic acid or essential fatty acid deficiency. J Clin Invest 65: 227–230PubMedCrossRefGoogle Scholar
  11. 11.
    Flick M, Perel A, Staub N (1981) Leukocytes are required for increased lung microvascular permeability after micro-embolization in sheep. Circ Res 48: 344–351PubMedGoogle Scholar
  12. 12.
    Freeman BA, Crapo JD (1982) Biology of disease: free radicals and tissue injury. Lab Invest 47: 412–426PubMedGoogle Scholar
  13. 13.
    Garrett RC, Thomas HM (1983) Meclofenamate uniformly decreases shunt fraction in dogs with lobar atalectasis. J Appl Physiol 54 (l): 284–289PubMedGoogle Scholar
  14. 14.
    Greene R, Lind S, Jantsch H (1987) Pulmonary vascular obstruction in severe ARDS: angiographic alterations after IV fibrinolytic therapy. Am J Radiol 148: 501–508Google Scholar
  15. 15.
    Halushka PV, Reines HD, Barrow SE et al. (1985) Elevated 6-keto-prostaglandin Fla in patients in septic shock. Crit Care Med 13: 451–453PubMedCrossRefGoogle Scholar
  16. 16.
    Harvey CF, Sugerman HJ, Tatum JL et al. (1987) Ibuprofen and methylprednisolone in a pig Pseudomonas ARDS model. Circ Shock 21: 175–183PubMedGoogle Scholar
  17. 17.
    Holcroft JW, Vassar MJ, Weber, CJ (1986) Prostaglandin E2 and survival in patients with the adult respiratory distress syndrome. Ann Surg 203: 371–378PubMedCrossRefGoogle Scholar
  18. 18.
    Jacobs ER, Bone RC (1983) Mediators of septic lung injury. Clin Chest Med 67: 701–715Google Scholar
  19. 19.
    Janoff A, White R, Carp H, Harel S, Demling R, Lee D (1979) Lung injury induced by leukocyte proteases. Am J Pathol 97: 111–135PubMedGoogle Scholar
  20. 20.
    Matthay MA, Eschenbacher WL, Goetzl EJ (1984) Elevated concentrations of leukotriene D4 in pulmonary edema fluid of patients with ARDS. J Clin Immunol 4: 479–483PubMedCrossRefGoogle Scholar
  21. 21.
    Meyrick BO, Brigham KL (1983) Acute effects of E. coli endotoxin on the pulmonary microcirculation of anesthetized sheep: structure-function relationships. Lab Invest 48: 458–470Google Scholar
  22. 22.
    Meyrick BO, Brigham KL (1984) Effect of single infusion of zymosan activated plasma on the pulmonary microcirculation of sheep: structure-function relationships. Am J Pathol 114: 32–45PubMedGoogle Scholar
  23. 23.
    Milligan SA, Hoeffel SA, Goldstein IM, Flick MR (1988) Effect of catalase on endotoxin-induced acute lung injury in unanesthetized sheep. Am Rev Respir Dis 137: 420–428PubMedGoogle Scholar
  24. 24.
    Modig J (1986) Adult respiratory distress syndrome. Acta Chir Scand (1986) 152: 241–249PubMedGoogle Scholar
  25. 25.
    Ogletree ML, Begley CJ, King GA, Brigham KL (1986) Influence of steroidal and nonsteroidal antiinflammatory agents on the accumulation of arachidonic acid metabolites in plasma and lung lymph after endotoxemia in awake sheep. Am Rev Respir Dis 133: 55–61PubMedGoogle Scholar
  26. 26.
    Reines HD, Halushka PV, Cook JA, Wise WC, Rambo W (1982) Plasma thromboxane concentrations are raised in patients dying with septic shock. Lancet ii: 174–75Google Scholar
  27. 27.
    Robbins RA, Russ WD, Rasmussen JK, Clayton MM (1987). Activation of the complement system in the adult respiratory distress syndrome. Am Rev Respir Dis. 135: 651–658PubMedGoogle Scholar
  28. 28.
    Shoemaker WC, Appel PL (1986) Effects of prostaglandin E1 in adult respiratory distress syndrome. Surgery 99: 275–282PubMedGoogle Scholar
  29. 29.
    Snapper JR, Hutchison AA, Ogletree ML et al. (1983) Effects of cyclooxygenase inhibitors on the alterations in lung mechanics caused by endotoxemia in the unanesthetized sheep. J Clin Invest 72: 63–76PubMedCrossRefGoogle Scholar
  30. 30.
    Snapper JR, Hinson JM, Hutchison A A, Lefferts PL, Ogletree ML, Brigham KL (1984) Effects of platelet depletion on the unanesthetized sheep’s pulmonary response to endotoxemia. J Clin Invest 74: 1782–1791PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Limited 1992

Authors and Affiliations

  • P. E. Wright
  • G. R. Bernard
  • K. L. Brigham

There are no affiliations available

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